The placebo effect occurs when people are given an inactive drug or therapy, but whose symptoms improve anyway.

Some people think this an amazing aspect of human physiology. Others think it's an illusion arising from the way clinical trials are run.

The issue is important as researchers often compare new drugs to placebo to gauge the true benefit of a therapy.

"Placebo effects probably form part of brain mechanisms involved in the resiliency of the organism to respond to environmental events (eg, injury, etc) and not biases in reporting," says Dr Jon-Kar Zubieta from the University of Michigan, Ann Arbor.

"Further understanding of these mechanisms would help harness them for innovative treatment strategies."

In pain

Zubieta and colleagues examined the effect of deep sustained pain with or without a placebo in young male volunteers.

They did this by infusion a 5% hypertonic saline solution into the masseter muscle, a large muscle used to raise the lower jaw that allows us to chew food.

The researchers used positron emission tomography (PET) and molecular imaging to examine whether introducing a placebo with the expectation of pain relief activates the brain to produce opiate-like substances.

Introducing the placebo reduced the sensation of pain, the team reports. There were higher ratings of pain relief and an increase in the rate of painful stimulus required to maintain the same level of pain.

The changes in the sensation of pain intensity correlated with mu-opioid system activation in different parts of the brain.

Direct evidence

The study provides the "first direct evidence" that the administration of a placebo with presumed analgesic properties activates pain and stress inhibitory systems in the brain "through direct effects on the mu-opioid receptors", the investigators write.

"The results ... are consistent with the notion that placebo-responding regions and neurochemical systems are an intrinsic part of neuronal processes that mediate the interaction between positive environmental conditions [in the present case the suggestion of analgesia] and the corresponding physical and emotional responses of the individual," the researchers conclude.

"We are now looking at individual differences in the placebo response, why some individuals have a more profound response than others, for example, the effects of gender, hormones and genes," Zubieta says.